Glucocorticosteroids Inhibit Leukotriene Production

Crocker, I.C.; Zhou, Chang Yi; Bewtra, Againdra K.; Kreutner, William; Townley, Robert G.

doi:10.1016/s1081-1206(10)63238-3

Cited by 44 publications

(19 citation statements)

References 28 publications

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“…LTE4 concentrations in BAL are not affected by high doses of oral steroids [25] and inhaled corticosteroids have no effect on urinary LTE4 excretion after allergen challenge [27]. It has been suggested that some mediators present in vivo, such as interleukin 3, modulate susceptibility to corticosteroids [28]. Even though the present study was limited by the single-blind design, the reduction observed in FENO values after montelukast treatment and the rebound following its washout period in patients on long-term treatment with ICS supports the anti-inflammatory effect of LTRAs and their complementary action to that of steroids, as recently reported by LIPWORTH et al [29] and BISGAARD et al [5].…”

Section: Discussionmentioning

confidence: 99%

Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children

Ghiro

Zanconato²,

Rampon³

et al. 2002

Eur Respir J

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Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children. L. Ghiro, S. Zanconato, O. Rampon, V. Piovan, M. F. Pasquale, E. Baraldi. #ERS Journals Ltd 2002. ABSTRACT: The aim of this prospective, self-controlled, single-blind study was to assess the effect of montelukast added to maintenance therapy with inhaled corticosteroids (ICS) on fractional exhaled nitric oxide (FENO) in asthmatic children.Thirty-five children (age 11.2¡0.4 yrs (mean¡SEM)) with mild-to-moderate persistent asthma treated with low to medium doses of ICS and FENOw20 parts per billion (ppb) were included. The patients were randomly assigned to two groups: 17 patients continued ICS (group C) and 18 had montelukast added to ICS for 3 weeks (group M). FENO measurements were performed in both groups at baseline (T1) and after 3 weeks (T2), and in group M also after 2 weeks of washout. FENO was measured by a chemiluminescence analyser using an on-line method (50 mL?s -1 ) with nitric oxide-free air. The overall mean daily dose of ICS was equivalent to 530¡58 mg?day -1 of beclomethasone in group M and to 564¡55 mg?day -1 of beclomethasone in group C. There were no significant differences in baseline FENO and forced expiratory volume in one second (FEV1) between the two groups. After 3 weeks there was a significant reduction of FENO values in patients of group M (T1 52.2¡7.8 ppb, T2 36.1¡4.6 ppb) but no significant changes in group C (T1 43.5¡6.0 ppb, T2 47.8¡9.4 ppb). In group M after 2 weeks of montelukast withdrawal, FENO rose to baseline values (55.6¡8.7 ppb).In conclusion, after montelukast treatment there is a fractional exhaled nitric oxide reduction in asthmatic children receiving maintenance therapy with inhaled corticosteroids. This suggests an anti-inflammatory effect of montelukast additive to that of inhaled corticosteroids. Fractional exhaled nitric oxide (FENO) has been proposed as a simple and noninvasive marker of airway inflammation in asthmatic patients [1]. Several studies have demonstrated that FENO in asthmatics is reduced by corticosteroid therapy [1,2], and that changes in FENO due to steroid dose changes precede the improvement or worsening in asthma symptoms and lung function [1]. Recently FENO was demonstrated to be useful in predicting loss of control in asthmatic subjects when inhaled corticosteroids (ICS) were withdrawn [3], with a positive predictive value similar to that obtained using sputum eosinophils and airway hyperresponsiveness, but with the advantage that FENO is an easier-to-measure, real-time parameter. This evidence suggests that FENO measurement reflects control of asthma and may help the physician in modulating anti-inflammatory therapy [1].The cysteinyl leukotrienes (Cys-LT) C4 and E4 play a key role in the pathophysiology of asthma [4]. The leukotriene receptor antagonists (LTRAs) that have recently been developed selectively block the binding of Cys-LT to the CysLT1 receptor, which has been identified as the receptor through which most their actions...

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Section: Discussionmentioning

confidence: 99%

Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children

Ghiro

Zanconato²,

Rampon³

et al. 2002

Eur Respir J

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“…GC inhibits the maturation, cytokine production, FceRI expression and mediator release of mast cells [46,47]. GC inhibits histamine release from basophils [48,49], induces apoptosis of eosinophils [50] and reduces the recruitment of antigen-presenting cells such as Langerhans cells [51].…”

Section: Cellular Level (Fig 2)mentioning

confidence: 99%

Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis

Okano

2009

Clinical and Experimental Immunology

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SummaryAllergic rhinitis is a common airway disease characterized by hypersensitivity, exudation, hypersecretion, inflammatory cell infiltration and remodelling. Intranasal glucocorticosteroids are the most effective drugs for controlling the inflammation caused by allergic rhinitis. Glucocorticosteroids exert anti-inflammatory effects through at least two pathways: the transactivation pathway and the transrepression pathway. Glucocorticosteroids also exert regulatory functions by inducing regulatory cytokines and forkhead box P3 (FoxP3 + ) regulatory T cells. Evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1 receptor antagonists, intranasal glucocorticosteroids can improve impaired performance symptoms, such as daytime sleepiness, associated with allergic rhinitis. Recent studies suggest that intranasal glucocorticosteroids might also be useful for the prophylactic treatment of pollinosis; this possibility is supported by the molecular mechanism of the anti-inflammatory action of glucocorticosteroids. These findings suggest that intranasal glucocorticosteroids might be positioned as first-line drugs for the treatment of both perennial and seasonal allergic rhinitis.

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“…Glucocorticoids are thought to exert this effect by lipocortinbinding of phospholipids to prevent access to PLA 2 . 79,80 However, as illustrated below, the effects of corticosteroids on LT synthesis in vitro often differ from those shown in vivo. In most in vitro studies, corticosteroids reduced CysLT production, while such effects are not always seen in in vivo studies.…”

Section: Targeting the Cysltsmentioning

confidence: 99%

“…84 The reasons for the discrepancies between the in vitro and in vivo effects of glucocorticoids on CysLTs are unclear. Crocker et al 80 and Kurimoto et al 85 suggested that glucocorticoids may modulate their effects on CysLT indirectly through other mediators. Another possible explanation may be that urinary CysLT levels, frequently measured to determine the effect of an agent on the lipoxygenase pathway, do not reflect the antiinflammatory effect of glucocorticoids in the lung.…”

Section: Targeting the Cysltsmentioning

confidence: 99%

Role of leukotrienes in asthma pathophysiology

Bisgaard

2000

Pediatr. Pulmonol.

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Glucocorticosteroids Inhibit Leukotriene Production

Cited by 44 publications

References 28 publications

Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children

Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children

Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis

Role of leukotrienes in asthma pathophysiology

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